Clinical trials of CRISPR gene editing technology have already started in the United States but, so far, the actual editing of cells has taken place in the lab. Cells have been harvested from patients, CRISPR has been used to perform edits to genes in the lab, and the edited cells have then been reintroduced back into patients. The treatment has been shown to be effective and safe, but it was not known if CRISPR would be effective if the edits were performed inside patients’ bodies. Now, for the first time, a clinical trial is being conducted where edits to genes are taking place in vivo.
The BRILLIANCE Trial is using CRISPR-Cas9 to treat patients with an inherited form of blindness called Leber congenital amaurosis (LCA). LCA is an eye disorder affecting around 1 in 80,000 individuals, which makes it the most common form of inherited sight loss. Patients with LCA lose their vision due to inhibition of production of light-sensing proteins in photoreceptor cells, which stops the cells from functioning properly.
There are around 20 different forms of LCA, each of which is caused by a different genetic mutation in one of three genes. There are no approved treatments for most forms of LCA. The only approved treatment is gene replacement therapy for a form of LCA caused by a mutation on the RPE65 gene.
The CRISPR clinical trial is being performed on patients with a rare form of the disease, LCA10, which is caused by a mutation on the CEP290 gene. Replacement gene therapy cannot be used to treat this form of LCA because the viral vectors used to introduce a functioning gene are too small to transport CEP290 into cells.
CRISPR has been shown to be safe and it allows genes to be edited with precision, but there is still potential for off-target effects – unintended edits at off-target locations. Those edits could potentially have deleterious effects, not just in the location where CRISPR is introduced, but also in other parts of the body, such as the liver. In the lab, researchers have greater controls, but the risk increases if the edits are performed inside the body. For patients with LCA10, there is no other option apart from performing the edits in vivo.
“For something like sickle cell disease, it’s possible to do the editing on cells in the lab and then the corrected bone marrow can be reinfused,” said trial investigator, Eric Pierce, MD, PhD, of Massachusetts Eye and Ear and Harvard Medical School in Boston. “We can’t do that for other organs in the body and the retina is one of them because it’s part of the central nervous system.”
In the trial, CRISPR is delivered via a subretinal injection. It is too early to tell whether the treatment will be a success. So far, only one patient has been treated. In total, 18 adult and pediatric patients will be treated using this new technique. The trial is due to be completed by 2024.
Further information on the clinical trial can be found on this link.